In many biomedical applications, laser light is used to induce fluorescence from biomolecules or biological substances that are studied. For example, such substances may include genes, proteins, cells and tissue. In some cases, scattering or absorption of the light is also employed in the measurements. The fluorescence is typically generated by means of a fluorophore or “biomarker” that has been chemically attached to the substances to be studied. Such fluorophores may, for example, be fluorescent proteins or dyes. The fluorophores often require excitation at a specific wavelength of light.
There is currently a trend on the biomedical instrumentation market to go from large and expensive analytical tools for research labs to more bench-top-like instruments that can address a larger range of customers. The goal for many instrument manufacturers is to move from medical research (understanding a disease) to drug development (ability to treat a disease) to clinical diagnosis (identify the disease and provide treatment). This trend is supported by the increased availability of increasingly compact and efficient laser sources. Many of the current fluorophores and instrumentation technologies have been developed around gas lasers (e.g. Argon, Krypton, Helium-Neon, Helium-Cadmium, Nitrogen) that have been available on the market since more than 30 years. However, such gas lasers suffer from large size, high energy consumption and short lifetime. The development of more compact solid-state laser alternatives enables instrument manufacturers to build smaller, more powerful and more robust systems, targeting larger-volume markets. This is an important growth driver in the biotech field and the overall market for solid-state lasers in general.
One requirement for the new solid-state lasers is to match the wavelengths provided by the gas lasers, since shifted wavelengths would require development of completely new fluorophores. In addition, it is desirable that the laser technology should be scalable in power, because higher powers are generally needed in order to reach higher resolutions and higher processing speeds.
Most of the currently used fluorophores are excited using light within the visible range of the electromagnetic spectrum. However, there is a growing demand for excitation in the ultraviolet range, e.g. for stem cell research and for increased DNA content resolution. Fluorophores that require excitation in the ultraviolet include, for example, DAPI, PE and Hoechst Blue. The use of these fluorophores is of particular interest in flow cytometry and confocal microscopy. The ideal excitation wavelength for these fluorophores is about 340-360 nm.
Light in the wavelength range around 350-365 nm can, as a first example, be obtained from Argon/Krypton gas lasers. However, as explained above, such gas lasers are typically rather bulky and suffer from a large energy consumption and short operating lifetime.
Another alternative to obtain the required excitation light could be to use a solid-state laser. One such conceivable approach for obtaining ultraviolet excitation light is to use GaN-based diode lasers emitting at 375 nm, but such lasers suffer from insufficient performance in terms of beam quality and lifetime. Another problem of such diode lasers is that the emission Wavelength of about 375 nm is slightly too long for optimal excitation.
Wavelength converted diode-pumped solid-state lasers (DPSSLs) are also potentially possible sources of excitation light in the ultraviolet wavelength range. However, in order to reach a reasonable conversion efficiency for the wavelength conversion, such lasers typically need to be pulsed.
For example, a DPSSL may be Q-switched in order to produce pulses of high power, such that frequency conversion into the ultraviolet range can be made with a fairly good conversion efficiency. However, Q-switched lasers are not suitable for many of the targeted biomedical applications due to their non-continuous character, leading to poor resolution in many cases.
An alternative to a Q-switched laser could be a mode locked laser. Mode locked lasers are sometimes referred to as being quasi-continuous, in the sense that the repetition rate for the output pulses is so high that, for many applications, it can be considered almost continuous. Mode locked lasers emit pulses of rather high power, that could be sufficient for practical frequency conversion into the ultraviolet. However, a mode locked laser is a comparatively complex laser system, which makes it bulky and expensive.
In view of the foregoing, it can be appreciated that a novel source of ultraviolet laser light is needed. In particular, it would be beneficial to have a compact laser that is capable of emitting continuous-wave laser light at reasonable powers for wavelengths below 400 nm.